The epigenetic modulation of alcohol/ethanol and cannabis exposure/co-exposure during different stages

Studies have reported the significant economic impact of smoking cannabis and drinking alcohol In the USA. It was estimated that the costs of cannabis-related treatment, hospitalization and loss of work-related pay have amounted to $200 billion. (Andersen AM, Dogan MV, Beach SRH, Philibert RA. 2015 Genes 6, 991–1022. (doi:10.3390/genes6040991)). Data from the National Epidemiologic Survey on Alcohol and Related Conditions showed that individuals with general anxiety disorder and substance use disorder (GAD-SUD) have higher psychiatric comorbidity rates than those without substance use disorder (Alegría AA, Hasin DS, Nunes EV, Liu SM, Davies C, Grant BF, Blanco C. 2010 J. Clin. Psychiatry 71, 1187–1195. (doi:10.4088/JCP.09m05328gry)). Moreover, the criminal justice system is significantly impacted by this cost (Andersen AM, Dogan MV, Beach SRH, Philibert RA. 2015 Genes 6, 991–1022. (doi:10.3390/genes6040991)). Despite the increasing use of cannabis, there are still too many obscure facts. One of the new areas that scientific evidence shows is impacted negatively by cannabis use is the epigenome, which is an understudied area that we are still learning about. In addition, over the past few decades, we have seen various social and healthcare changes that have raised critical questions about their ongoing roles in regulating marijuana and alcohol use. This is important because of the increasing popularity and usage across various ages especially young adults and teenagers. More than 97.5 million Americans over 12 years old have used cannabis for non-medical use despite the significant side effects, with 1 in 10 users developing cannabis dependence (Crean RD, Crane NA, Mason BJ. 2011 J. Addict. Med. 5, 1–8. (doi:10.1097/ADM.0b013e31820c23fa), Office of Applied Studies. 2006 Substance Abuse and Mental Health Services Administration, USA.). It was reported that 16% of substance abuse admissions in the USA were for cannabis-related symptoms, which is second only to alcohol-related disorders (Agalioti T, Lomvardas S, Parekh B, Yie J, Maniatis T, Thanos D. 2000 Cell 103, 667–678. (doi:10.1016/S0092-8674(00)00169-0), Soutoglou E, Talianidis I. 2002 Science 295, 1901–1904. (doi:10.1126/science.1068356)). Today there are thirty-one states and the District of Columbia that currently have legalized marijuana for either medical or recreational use. Data about marijuana use from NIAAA's National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) indicates that ‘in total, 79 000 people were interviewed on alcohol and drug use. When examined by age young adults (ages 18–21) were found to be at highest risk for marijuana use and marijuana use disorder, with use increasing from 10.5 to 21.2% and disorder increasing from 4.4 to 7.5%’. ‘Given these facts, George Koob, PhD, director of NIAAA stated the importance for the scientific community to convey this information to the public about the potential hazards of marijuana and it's use’. On the other hand, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from alcohol use disorders. To the best of our knowledge, epigenetic mechanisms have been previously studied in alcohol and cannabis abuse separately. Recent studies highlighted the molecular mechanisms that are linked with drug-induced transcriptional regulation, behavioural abnormalities and neurodegeneration, which has emphasized the role of chromatin modification/remodelling in the generation of drug activation of certain genes and the disabling of others, and the effect of that on addiction (Maze I, Nestler EJ. 2011 Ann. N. Y. Acad. Sci. 1216, 99–113. (doi:10.1111/j.1749-6632.2010.05893.x); Renthal W, Nestler EJ. 2008 Trends Mol. Med. 14, 341–350. (doi:10.1016/j.molmed.2008.06.004)). In this review, we will give an overview of epigenome science relevant to cannabis/the endocannabinoid system and the potential of epigenetic overlap between alcohol and cannabinergic activity at different stages, to aid further investigations that could bring more treatment options to our horizon.